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Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection
Open accessAbstract
Background & aims There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.Methods CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.Results In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.Conclusion CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
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“CA19–9 elevations can be observed in plasma samples obtained in the pre-diagnostic setting, suggesting a potential window of opportunity for early detection38.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [38]
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Cites
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21492 · Cited by 84,109
DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649
Statistical Methods in Cancer Research
Breslow, N. E. (1980) · Cited by 7,332
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202
Detection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., et al. (2018) · Science · doi:10.1126/science.aar3247 · Cited by 2,783
Self-citationInternational consensus guidelines 2012 for the management of IPMN and MCN of the pancreas
Tanaka, M., Fernández-del Castillo, C., Adsay, V., Chari, S., Falconi, M., Jang, J.-Y., Kimura, W., Levy, P., Pitman, M. B., Schmidt, C. M., et al. (2012) · Pancreatology · doi:10.1016/j.pan.2012.04.004 · Cited by 2,354
Self-citationRyan, D. P., Hong, T. S., & Bardeesy, N. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1404198 · Cited by 2,348
Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors
Rawla, P., Sunkara, T., & Gaduputi, V. (2019) · World Journal of Oncology · doi:10.14740/wjon1166 · Cited by 2,269
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982
Liu, M. C., Oxnard, G. R., Klein, E. A., Swanton, C., Seiden, M. V., Liu, M. C., Oxnard, G. R., Klein, E. A., Smith, D., Richards, D., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.02.011 · Cited by 1,495
Self-citationTherapeutic developments in pancreatic cancer: current and future perspectives
Neoptolemos, J. P., Kleeff, J., Michl, P., Costello, E., Greenhalf, W., & Palmer, D. H. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0005-x · Cited by 1,170
Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial
Prorok, P. C., Andriole, G. L., Bresalier, R. S., Buys, S. S., Chia, D., Crawford, E. D., Fogel, R., Gelmann, E. P., Gilbert, F., Hasson, M. A., et al. (2000) · Controlled Clinical Trials · doi:10.1016/s0197-2456(00)00098-2 · Cited by 1,038
Prevalence of Unsuspected Pancreatic Cysts on MDCT
Laffan, T. A., Horton, K. M., Klein, A. P., Berlanstein, B. P., Siegelman, S. S., Kawamoto, S., Johnson, P. T., Fishman, E. K., & Hruban, R. H. (2008) · American Journal of Roentgenology · doi:10.2214/ajr.07.3340 · Cited by 882
Rothman, K. J., Greenland, S., & Lash, T. L. (2008) · Encyclopedia of Quantitative Risk Analysis and Assessment · doi:10.1002/9780470061596.risk0599 · Cited by 706
Ballehaninna, U. K., & Chamberlain, R. S. (2012) · PubMed · doi:10.3978/j.issn.2078-6891.2011.021 · Cited by 704
Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention
Lennon, A. M., Buchanan, A. H., Kinde, I., Warren, A., Honushefsky, A. M., Cohain, A. T., Ledbetter, D. H., Sanfilippo, F. P., Sheridan, K. M., Rosica, D., et al. (2020) · Science · doi:10.1126/science.abb9601 · Cited by 665
Prevalence of incidental pancreatic cysts in the adult population on MR imaging
Lee, K. S., Sekhar, A., Rofsky, N. M., & Pedrosa, I. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.122 · Cited by 610
Cohen, J. D., Javed, A. A., Thoburn, C. J., Wong, F., Tie, J., Gibbs, P., Schmidt, C. M., Yip-Schneider, M., Allen, P. J., Schattner, M. A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704961114 · Cited by 588
Self-citationNew-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer
Pannala, R., Basu, A., Petersen, G. M., & Chari, S. T. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70337-1 · Cited by 577
Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death
Kovalchik, S. A., Tammemägi, M. C., Berg, C. D., Caporaso, N. E., Riley, T. L., Korch, M., Silvestri, G. A., Chaturvedi, A. K., & Katki, H. A. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301851 · Cited by 570
Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis
Kirkegård, J., Mortensen, F. V., & Cronin-Fenton, D. P. (2017) · The American Journal of Gastroenterology · doi:10.1038/ajg.2017.218 · Cited by 551
Murphy, J. E., Wo, J. Y.-L., Ryan, D. P., Jiang, W., Yeap, B. Y., Drapek, L. C., Blaszkowsky, L. S., Kwak, E. L., Allen, J. N., Clark, J. W., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.0329 · Cited by 534
High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations
de Jong, K., Nio, C. Y., Hermans, J. J., Dijkgraaf, M. G. W., Gouma, D. J., van Eijck, C. H. J., van Heel, E., Klaß, G., Fockens, P., & Bruno, M. J. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2010.05.017 · Cited by 533
Early detection of pancreatic cancer
Pereira, S. P., Oldfield, L., Ney, A., Hart, P. A., Keane, M. G., Pandol, S. J., Li, D., Greenhalf, W., Jeon, C. Y., Koay, E. J., et al. (2020) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30416-9 · Cited by 482
Kromrey, M., Bülow, R., Hübner, J., Paperlein, C., Lerch, M. M., Ittermann, T., Völzke, H., Mayerle, J. V., & Kühn, J. (2017) · Gut · doi:10.1136/gutjnl-2016-313127 · Cited by 433
Canto, M. I., Almario, J. A., Schulick, R. D., Yeo, C. J., Klein, A., Blackford, A., Shin, E. J., Sanyal, A., Yenokyan, G., Lennon, A. M., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.05.035 · Cited by 414
The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates
Poruk, K. E., Gay, D., Brown, K. S., Mulvihill, J. D., Boucher, K. M., Scaife, C. L., Firpo, M. A., & Mulvihill, S. J. (2013) · Current Molecular Medicine · doi:10.2174/1566524011313030003 · Cited by 396
Model to determine risk of pancreatic cancer in patients with new-onset diabetes
Sharma, A., Kandlakunta, H., Nagpal, S. J. S., Feng, Z., Hoos, W., Petersen, G. M., & Chari, S. T. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.05.023 · Cited by 394
AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review
Aslanian, H. R., Lee, J. H., & Canto, M. I. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.03.088 · Cited by 317
Precursors to Invasive Pancreatic Cancer
Maitra, A., Fukushima, N., Takaori, K., & Hruban, R. H. (2005) · Advances in Anatomic Pathology · doi:10.1097/01.pap.0000155055.14238.25 · Cited by 290
Self-citationBlackford, A. L., Canto, M. I., Klein, A. P., Hruban, R. H., & Goggins, M. (2020) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djaa004 · Cited by 270
Serum CA 19-9 as a Biomarker for Pancreatic Cancer—A Comprehensive Review
Ballehaninna, U. K., & Chamberlain, R. S. (2011) · Indian Journal of Surgical Oncology · doi:10.1007/s13193-011-0042-1 · Cited by 239
Steinberg, W. M., Gelfand, R., Anderson, K. K., Glenn, J. D., Kurtzman, S. H., Sindelar, W. F., & Toskes, P. P. (1986) · Gastroenterology · doi:10.1016/0016-5085(86)90930-3 · Cited by 213
O'Brien, D. P., Sandanayake, N. S., Jenkinson, C., Gentry-Maharaj, A., Apostolidou, S., Fourkala, E.-O., Camuzeaux, S., Blyuss, O., Gunu, R., Dawnay, A., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0365 · Cited by 200
Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases
Kim, S., Park, B. K., Seo, J. H., Choi, J., Choi, J. W., Lee, C. K., Chung, J. B., Park, Y., & Kim, D. W. (2020) · Scientific Reports · doi:10.1038/s41598-020-65720-8 · Cited by 193
The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates
Poruk, K. E., Gay, D. Z., Brown, K., et al. (2013) · Current Molecular Medicine · doi:10.2174/156652413805076876 · Cited by 182
Petersen, G. M. (2016) · Seminars in Oncology · doi:10.1053/j.seminoncol.2016.09.002 · Cited by 157
Tang, R. S. Y., Weinberg, B., Dawson, D. W., Reber, H. A., Hines, O. J., Tomlinson, J. S., Chaudhari, V. V., Raman, S. S., & Farrell, J. J. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.04.005 · Cited by 155
Jacobs, E. J., Chanock, S. J., Fuchs, C. S., LaCroix, A., McWilliams, R. R., Steplowski, E., Stolzenberg‐Solomon, R. Z., Arslan, A. A., Bueno‐de‐Mesquita, H. B., Gross, M., et al. (2010) · International Journal of Cancer · doi:10.1002/ijc.25148 · Cited by 151
Self-citationSequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer
Capello, M., Bantis, L. E., Scélo, G., Zhao, Y., Peng, L., Dhillon, D. S., Patel, N. J., Kundnani, D. L., Wang, H., Abbruzzese, J. L., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw266 · Cited by 148
Self-citationCloyd, J. M., Katz, M. H. G., Prakash, L., Varadhachary, G. R., Wolff, R. A., Shroff, R. T., Javle, M. M., Fogelman, D. R., Overman, M. J., Crane, C. H., et al. (2016) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-016-3265-1 · Cited by 141
Self-citationJang, J.-Y., Park, T., Lee, S., Kang, M. J., Lee, S. Y., Lee, K. B., Chang, Y. R., & Kim, S.-W. (2014) · British journal of surgery · doi:10.1002/bjs.9491 · Cited by 132
A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer
Fahrmann, J. F., Bantis, L. E., Capello, M., Scelo, G., Dennison, J. B., Patel, N., Murage, E., Vykoukal, J., Kundnani, D. L., Foretova, L., et al. (2019) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djy126 · Cited by 115
Self-citationChoi, S. H., Park, S. H., Kim, K. W., Lee, J. Y., & Lee, S. S. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.03.020 · Cited by 104
Nolen, B. M., Brand, R. E., Prosser, D., Velikokhatnaya, L., Allen, P. J., Zeh, H. J., Grizzle, W. E., Lomakin, A., & Lokshin, A. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094928 · Cited by 94
Lewis antigen‑negative pancreatic cancer: An aggressive subgroup
Liu, C., Deng, S., Jin, K., Gong, Y., Cheng, H., Fan, Z., Qian, Y., Huang, Q., Ni, Q., Luo, G., et al. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.4989 · Cited by 80
Guo, M., Luo, G., Lu, R., Shi, W., He, C., Yu, L., Jin, K., Yang, C., Wang, Z., Long, J., et al. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12278 · Cited by 78
Self-citationKhoury, R. E., Kabir, C., Maker, V. K., Banulescu, M., Wasserman, M., & Maker, A. V. (2018) · Annals of Surgical Oncology · doi:10.1245/s10434-018-6425-6 · Cited by 77
Advances in Biomarker Research for Pancreatic Cancer
Bhat, K., Wang, F., Ma, Q., Li, Q., Mallik, S., Hsieh, T., & Wu, E. (2012) · Current Pharmaceutical Design · doi:10.2174/13816128112092439 · Cited by 74
Ohno, E., Hirooka, Y., Kawashima, H., Ishikawa, T., Kanamori, A., Ishikawa, H., Sasaki, Y., Nonogaki, K., Hara, K., Hashimoto, S., et al. (2017) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13967 · Cited by 70
Honda, K., Katzke, V. A., Hüsing, A., Okaya, S., Shoji, H., Onidani, K., Olsen, A., Tjønneland, A. M., Overvad, K., Weiderpass, E., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31900 · Cited by 60
Fahrmann, J. F., Mao, X., Irajizad, E., Katayama, H., Capello, M., Tanaka, I., Kato, T., Wistuba, I. I., Maitra, A., Ostrin, E. J., et al. (2020) · Cancers · doi:10.3390/cancers12051147 · Cited by 34
Self-citationKim, J., Yuan, C., Babić, A., Bao, Y., Clish, C. B., Pollak, M., Amundadottir, L. T., Klein, A. P., Stolzenberg‐Solomon, R. Z., Pandharipande, P. V., et al. (2020) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-19-1389 · Cited by 29
Self-citationPancreatic cysts in general population on ultrasonography: Prevalence and development of risk score
Soroida, Y., Sato, M., Hikita, H., Hagiwara, S., Sato, M., Gotoh, H., Kato, S., Iwai, T., Yamazaki, T., Yatomi, Y., et al. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1196-y · Cited by 22
Kobayashi, M., Katayama, H., Irajizad, E., Vykoukal, J. V., Fahrmann, J. F., Kundnani, D. L., Yu, C., Cai, Y., Hsiao, F. C., Yang, W., et al. (2020) · Cancers · doi:10.3390/cancers12020485 · Cited by 12
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Wood, L. D., Canto, M. I., Jaffee, E. M., & Simeone, D. M. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.03.056 · Cited by 918
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Metadata
- Authors
- Fahrmann, J. F., Schmidt, C. M., Mao, X., Irajizad, E., Loftus, M., Zhang, J., Patel, N., Vykoukal, J., Dennison, J. B., Long, J. P., Do, K.-A., Zhang, J., Chabot, J. A., Kluger, M. D., Kastrinos, F., Brais, L., Babic, A., Jajoo, K., Lee, L. S., Clancy, T. E., Ng, K., Bullock, A., Genkinger, J., Yip-Schneider, M. T., Maitra, A., Wolpin, B. M., & Hanash, S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Indiana University School of Medicine (US)
- Harvard University (US)
- Columbia University Irving Medical Center (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Hanash, Samir
- ORCID
- Fahrmann, Johannes F.
- Schmidt, C. Max
- Mao, Xiangying
- Irajizad, Ehsan
- Loftus, Maureen
- Zhang, Jinming
- Dennison, Jennifer B.
- Long, James P.
- Do, Kim-Anh
- Zhang, Jianjun
- Kluger, Michael D.
- Kastrinos, Fay
- Brais, Lauren
- Lee, Linda S.
- Clancy, Thomas E.
- Ng, Kimmie
- Bullock, Andrea
- Genkinger, Jeanine
- Yip-Schneider, Michele T.
- Maitra, Anirban
- Wolpin, Brian M.
- Hanash, Samir
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 160
- Issue
- 4
- Pages
- 1373-1383.e6
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC8783758
- OpenAlex
- W3110895646
- Cited by
- 208
- References
- 56
- Citations by year
- 2026: 37 · 2025: 52 · 2024: 40 · 2023: 37 · 2022: 30 · 2021: 12
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- Pancreatic Cancer Action Network
- Lustgarten Foundation
- University of Texas MD Anderson Cancer Center
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- CA19-9, pancreatic cancer, early detection, liquid biopsy, circulating tumor markers, TIMP-1, LRG1, multimarker panels, pre-diagnostic biomarkers, chronic pancreatitis, pancreatic cysts, PLCO Cancer Screening Trial
- MeSH terms
- Liquid Biopsy, Aged, Diagnosis, Differential, Feasibility Studies, Female, Humans, Male, Mass Screening, Middle Aged, Pancreatic Cyst, Pancreatic Neoplasms, Sensitivity and Specificity, United States, CA-19-9 Antigen, Pancreatitis, Chronic, Early Detection of Cancer, Healthy Volunteers
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